Ryan P Taylor

GTx Inc. · Medical Affairs

Muscle wasting in cancer is a common and often occult condition that can occur prior to overt signs of weight loss and before a clinical diagnosis of cachexia can be made. Muscle wasting in cancer is an important and independent predictor of progressive functional impairment, decreased quality of life, and increased mortality. Although several ther...

Background: Historically, androgens have been utilized for the treatment of breast cancer (BC) as the androgen receptor (AR) is the most highly expressed steroid receptor in BC (75-95% of estrogen receptor positive (ER+) and 50% of ER negative). Reports of the use of androgens in metastatic BC (MBC) indicate that women progressing on tamoxifen have...

This review highlights selective androgen receptor modulators (SARMs) as emerging agents in late-stage clinical development for the prevention and treatment of muscle wasting associated with cancer. Muscle wasting, including a loss of skeletal muscle, is a cancer-related symptom that begins early in the progression of cancer and affects a patient's...

Reactive oxygen species (ROS) have been reported to play a primary role in triggering the cardioprotective adaptations by some preconditioning procedures, but whether they are required for exercise-induced preconditioning is unclear. Thus, in this study we used the free radical scavenger N-(2-mercaptopropionyl)glycine (MPG) to test the hypothesis t...

We tested the hypothesis that administration of the free radical scavenger N‐2‐mercaptopropionyl glycine (MPG) during exercise will prevent development of protection against ischemia‐reperfusion (I‐R) injury. Male, 4‐mo‐old, F344 rats were divided into sedentary controls (SED, n=7); sedentary plus 100 mg/kg MPG injection (SED/MPG, n=12); exercised...

The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched ( approximately 5-9 mo) CRYAB/HSPB2 double knockout...

It is now well established that exercise can result in cardioprotection against ischemia-reperfusion (I-R) injury; however, the adaptations within the heart that provide the protection are still in doubt. The cytoprotective proteins receiving the most attention to date are antioxidant enzymes and heat shock proteins. The extent of I-R injury is dep...

The autosomal dominant mutation in the human alphaB-crystallin gene inducing a R120G amino acid exchange causes a multisystem, protein aggregation disease including cardiomyopathy. The pathogenesis of cardiomyopathy in this mutant (hR120GCryAB) is poorly understood. Here, we show that transgenic mice overexpressing cardiac-specific hR120GCryAB reca...

The mediators of acute exercise-induced preconditioning against ischemia-reperfusion injury are not understood. This study assesses the role of nitric oxide synthase (NOS), a reported mediator of other forms of preconditioning. Male Fischer 344 rats were divided into five groups (n = 6-7): sedentary (Sed); exercised 2 days on a treadmill at 20 m/mi...

Synthesis of inducible heat shock protein 70 (HSP70) is impaired in aged animals following acute stresses including exercise. In this study we determined whether aging affects expression of this cytoprotective protein following chronic exercise participation. Male Fischer 344 rats, final ages 6 and 24 months, exercised identically for 10 weeks on a...

It is well established that participation in a chronic exercise program can reduce coronary heart disease (CHD) risk factors and improve myocardial tolerance to ischemia-reperfusion (I-R) injury. Low-intensity exercise programs are known to be effective in reducing CHD risk factors in humans and rats, but whether similar programs are of sufficient...

Small MW heat shock proteins (i.e. sHSPs approximately 15-30 kDa) share significant sequence similarity within the "alpha-crystallin domain" but exhibit different patterns of gene expression, transcriptional regulation, sub-cellular localization, and, perhaps, function. The chaperone-like properties of many sHSPs are defined biochemically by their...

For many years investigators have been researching methods of preconditioning the myocardium against ischaemia-induced damage; however, a majority of this research has been carried out in young animals and cells. Normal ageing is accompanied by changes in the human myocardium that decrease its capacity to tolerate and respond to various forms of st...

Exercise improves cardioprotection against ischemia-reperfusion in young animals but has not been investigated in older animals, which represent the population most likely to suffer an ischemic event. Therefore, we sought to determine the effects of aging on exercise-induced cardioprotection. Young, middle-aged, and old (4, 12, and 21 mo old) male...

The purpose of this study was to determine whether exercise training could precondition the myocardium against hydrogen peroxide (H(2)O(2))-induced damage. Male Fischer 344 rats ran on a treadmill for 9 weeks (60 min/day, 22 m/min, 6 degrees grade, 5 days/week). Isolated perfused working hearts from exercise trained (ET, n=8) and sedentary (SED, n=...

The aim of this study was to determine the effects of acute bouts of exercise on myocardial recovery after ischemia and heat shock protein expression. Adult female Sprague-Dawley rats were divided into five groups: 1) 1-day run (1DR; n = 6) and 2) 3-day run (3DR; n = 7), in which rats ran for 100 min at a speed of 20 m/min up a 6 degrees grade for...

The aim of this study was to determine the roles of exercise and the accompanying increase in body temperature on cardioprotection from an ischemia/reperfusion insult. Female Sprague-Dawley rats were divided into four groups: 1. Exercised in 24°C room (E-24°) for 100 minutes at a speed of 20 m/min up a 15% grade (n=6); 2. Exercised the same way in...